Metahydroxybenzylmethylcarbinamines and medicinal preparations comprising the same



Patented Oct. 31, 1944 MINES AND MEDICINAL COMPRISING THE PREPARATIONS v Gordon A. Alles, Los Angeles, Calif.

No Drawing. Application July 5, i938,

Serial No. 217,584

This invention relates to a new composition of matter, and more particularly a synthetic organic compound, and to a medicinal preparation comprising such compound. 1

This application is a continuation-in-part of my application Serial No. 167,414, filed October 5,1937, which has become abandoned.

The principal object of this invention is to provide a new composition of matter which may be used as an intermediate the synthetic production of compounds useful fortherapeutic purposes, or may itself be used as a medicinal preparation in the therapeutic treatment of-animals and man.

A particular object of the inventionis to provide a new and: useful medicinal preparation for use in the treatment of animals and man. a l The new composition in accordance with this invention will be found to have various uses as a. medicinal preparation, and from the standly or systemically, it will constrict the small blood vessels, stimulate the heart, relax the bronchi and intestines, orxdilate the pupil of the eye, in ways that; may be insome respects likened tothose of epinephrine: when acting upon these organs,

This new composition as av medicinal preparationain accordance. with this. invention may be employed, in. various forms and. may be various- 1y administered. Thus, for example, it may be wherein R represents. a member of the group consisting of hydrogen and a methyl radical. A specific embodiment of the invention comprises metahydroxybenzylmethylcarbinamine or a salt thereof, and another specific embodiment com- 5 Claims. (Cl. 260-5703.)

prises metahydroxybenzylmethylcarbinmethylamine or a salt thereof. In either of these embodimen'ts, the salts may be, for example, hydrochlorides, sulfates, oxalates, tartrates, etc.

It will? be understood that by reference to a metahydroxyben'zylmethylcarbinamine, in the following descriptions and claims, it is contemplated and intended that such term include from the broad standpoint, metahydroxybenzylmethylbinamine in accordance with this invention may be prepared by demeth-ylation of the corresponding metamethoxybenzylmethylcarbinamine having the. formula:

NHLR cin cn-cni Ute...

wherein R. represents a member of the group consisting of hydrogen and a methyl radical, methods of preparation of which. are fully described in my copending. patent. application. Ser.

No.2 217,583,. filed. concurrently herewith.

Byway of illustrating suitable methods for the preparation of a newcomposition in accordance with this invention, a descriptionof certain preparative methods and their specific productsv is herewith detailed:

Metahr drorybenzylmethylcarbinwmme.-This substance is very conveniently prepared by demethylation of metamethoxybenzylmethylcar. binam-ine by use of a concentrated hydrobromic acid solution. One-tenth gram-mol of metamethoxybenzylmethylcarbinamine is dissolved in one-tenth liter of 48% hydrobromic acid and heated to boiling. under a, reflux condenser for four hours and. then the excess hydrobromic acid distilled ofi. Addition. of some Water, and then sodium carbonate, to the residue causes separation of' a semi-solid precipitate whichis. taken up with butanol. treatment of theresidue with benzene gives a solid metahydroxybenzylmethylcarbinamine base which melts at C. I

' Metahydroxybenzylmethylcarbinamine salts.- The' hydrochloride and neutral sulfate arereadi ly, prepared by'treatingthe amine with an equivalent of hydrochloric or sulfuric acid but these salts appear extremely hygroscopic and are not readily obtained in solid form. A definite salt Evaporation of the butanol and and dextrotartaric acid dissolved in ethanol, followed by addition of ether, and the bitartrate so obtained melts at ISO-161 C.

therapeutic effect to be attained and the method in which the preparation is to be administered.

The bases or salts may be dissolved in or mixed with any suitable excipient, and the proportion of the bases or salts of the bases may be any proportion which is sufficient to impart effective therapeutic properties to the preparation. It

MetahydroxybenzyZmethgflcdrbinmethylamine-This substance is prepared from the corresponding metamethoxybenzylmethylcarbinmethylamine by treatment with concentrated gram-mol hydrobromic acid and the mixture heated to boiling for four hours and thenthe excess hydrowith more sodium carbonate, it is evaporated to a small volume and considerable anhydrous ether added. On standing in the refrigerator for some time, solid crystals of metahydroxybenzylmethylcarbinmethylamine come out and thesemelt at Metahydromyb e nay Z methylcarbinmethyla- I mine salts.'The sulfate is readily prepared by exact neutralization of ,the amine with an hydrobromic acid solution. One -twenty-fifth' equivalent of sulfuric acid but is difiicult to obtain as a solid because of its great avidity for taking up water from the-air. By preparing the amine and dextrotartaric acid in ethanol solution, followed by addition of ether, yielding a semi-solid and this on placing under a vacuum in a desiccator yields a solid, very hygroscopic bitartrate. 1

' As an example of the use'of the composition of this invention as an intermediate in the synthetic production of other organic compounds,

any of the embodiments thereotmay be methylated by known processes to yield the correspondingquaternary'ammonium salt,- such as meta- 2'.

hydroxybenzylmethylcarbintrimethylammonium iodide.

In using the broad and specific embodiments of this inventionas medicinal preparations, the bases or salts of the bases may be dissolved in water or other desired solvent, or mixed with liquid compositions, and applied locally by tampon or spray. Or, by way of another example, the bases or salts of the bases may be dissolved in an alcohol elixir for oral administration to afiect the circulation or to act more generally to simulate sympathetic nerve stimulation and results therefrom. Again, for example, a solid form may be prepared by tableting the salts of the bases alone or together with an agent like lactose and the tablets administered into the mouth or, after solution in water, by hypodermic injection. I l

The proportion, of the bases or salts of the bases in the medicinal preparations, and the nature and proportions of other ingredients used, are subject to wide variation, according the maybe as low as 1% or even less when used insolution, or as much as 50% or even as high as in other cases, as when used in solid tabletedform; The pure bases or salts of the bases may be used alone to give certain therapeutic effects, although it is often preferable to metamethoxybenzylmethylcarbin methylamine is dissolved in one-tenth'liter 48% add other constituents, as solvents or diluents,

to impart desired physical properties, perfume,

color, or the like to the liquid or solid preparation. Thus, a, medicinal preparation in accordance with this invention'may comprise the designated bases or salts, aloneor together with a suitable excipient. t I

By way of illustrating suitableproportions of active ingredient and forms of a medicinal remedy in accordance with this invention, description of some such medicinal products are herewithdetailed, in which the bases or :theirsalts are mixed with othersuitable ingredients as excipients r i Aqueous solutions for topical applicationto eye or nasal membranes are prepared by dissolving 1.00 g. metahydroxybenzylrnethylcarbinamine in cc. of water saturate d with boric acid, this water solution serving as an effective sterile diluting agency for the therapeutically active base.- q Sterile ampule vials containing dry metahy droxybenzylmethylcarbinmethylamine sulphate for preparation of solutions for parenteral inr iections-are filled with 20 mg; ofthev puresalt, or with'a mixture of 20 mg. .oi the pure salt and 9. mg. of sodium chloride, so that on use by addition. of, 1.0 cc. sterilev water a solution physiological in sodium chloride content is obtained. i q

Elixirs for oral administration of the salts of the bases are well prepared by dissolving 5 g. of the desired salt in 100 cc. water and adding cc. ethanol, 10 cc. of lemonfiavor'concentrate and 765 cc. of 60% simple sucrose syrup, which may be tinted with a certified dyestufi'.

Tablets for hypodermic solution preparations aremade as triturate tablets of 50 mg. metahydroxybenzylmethylcarbinamine bitartrate without admixture'of any other substance, while tablets for oral administration'are prepared by oompressinga granulated mixture of 20, 50 or 100 mg. of the same compound with 180, or 100 mg. respectively of lactose -which'may,.if desired, be flavored witha .trace of saccharin or similar substance. v

I-claim:

1. A metahydroxybenzylmethylcarbinamine of the group consisting of metahyd'roxybenzyb methylcarbinamine and salts thereof.

2. Meta-hydroxybenzylmethylcarbinamine.

3. A salt of metahydroxybenzylmethylcarbinamine.

4. Metahydroxybenzylmethylcarbinamine bitartrate.

5. Metahydroxybenzylmethylcarbinamine sulfate.

goanonn. ALLES. 

